Effect of Nifedipine on Tubular Handling of Uric Acid in Transplanted Kidney on Cyclosporine A Treatment

Abstract

Hyperuricemia resulting from tubular urate transport defects is a well-known nephrotoxic effect of cyclosporine A (CyA) on renal blood perfusion in organ recipients. The aim of this study was to define the mechanism of the tubular urate transport defect in hyperuricemic renal graft recipients on CyA and to evaluate the effect of nifedipine retard administration on this tubular dysfunction. Tubular uric acid transport was evaluated by the probenecid test in 17 hyperuricemic (group 1) and 6 normouricemic (group 2) renal graft recipients treated with CyA. Maximal urate excretion after probenecid administration was 25.5 ± 4.6 versus 42.5 ± 7.7% (p < 0.001) and postsecretory urate reabsorption was 79.2 ± 8.3 versus 78.5 ± 9.7% (NS), respectively. The effects of nifedipine retard on renal urate transport were evaluated in 6 hyperuricemic patients. Seven days of nifedipine therapy did not significantly decrease mean serum uric acid levels (7.7 ± 1.6 to 7.1 ± 1.1 mg/dl) nor increase urate clearance (3.8 ± 1.3 to 4.7 ± 1.6 ml/min/1.73 m²). The uricosuric effect of probenecid was manifested by an increase in tubular urate transport from 25.5 ± 4.6 to 37.3 ± 7.2%, p < 0.01, paralleled by an increase in postsecretory urate reabsorption from 20.5 ± 3.7 to 31.4 ± 5.7% (p < 0.003). Postsecretory reabsorption expressed as a percentage of secreted urate in both evaluations did not differ significantly (80.3 ± 6.2 vs. 84.4 ± 3.1%). These results suggest that hyperuricemia in kidney recipients on CyA is a consequence of decreased tubular urate secretion, and administration of nifedipine retard in these patients equally increased both tubular secretion and back-reabsorption of secreted uric acid.

Elevated serum uric acid levels in metabolic syndrome: an active component or an innocent bystander?

“…Calcium channel blockers (eg, amlodipine [153], felodipine [154]) significantly decrease SUA levels by increasing urate excretion. Nifedipine [155] and verapamil [156] are the only drugs from this category that seem to have a neutral effect on SUA levels.…”

Effect on Serum Uric Acid Levels of Drugs Prescribed for Indications other than Treating Hyperuricaemia

“…Another calcium channel blocker, manidipine has been shown to increase urate excretion, possibly by increasing creatinine clearance [69,70]. The older calcium channel blocker, nifedipine has a "neutral" effect on SUA levels [71][72][73][74].…”

A retrospective study of hyperurecemia in renal transplant recipients

“…Post operatively patients received cyclosporine, mycophenolate mofetil, azathioprin, sirolimus or tacrolimis. Cyclosporine and other calcinurin inhibitors are known causes of hyperuricemia 2,[29][30][31][32][33][34][35] . We found in this study that cyclosporine is associated with 76% of the patients with increase uric acid level.…”